Acute myeloid leukemia (AML), also called acute nonlymphocytic, granulocytic, myelocytic, myeloblastic, or myeloid leukemia, is a disease in which cancer cells develop in the blood and bone marrow. The cancer develops from two main types of immature white blood cells that normally develop into mature granulocytes or monocytes. The result is a malignancy characterized by the accumulation in blood and bone marrow of abnormal hematopoietic progenitors and disruption of normal production of erythroid, myeloid, and/or megakaryocytic cell lines. It can be subdivided morphologically into specific types depending on which cell lines are involved. AML subtypes (M0-M7) are determined by cell morphology with particular subtypes such as M3 (acute promyelocytic leukemia or APL) having a more favorable outcome:
M0: undifferentiated large granular;
M1 and M2: acute myeloblastic;
M3: acute promyelocytic;
M4: myelomonocytic;
M5: monocytic;
M6: erythroleukemia;
M7: megakaryocytic; and
M4Eo: eosinphils.
By classifying AML in this manner, developed treatments can more specifically eradicate the particular defective cell clone and hopefully provide a better outcome after therapy. However, the leukemia cell karyotype is more relevant for determination of appropriate therapeutic options.
Current AML therapy regimens generally involve two stages: Initial treatment (“induction therapy”) for AML is aimed at eradicating the leukemic clone to re-establish normal hematopoiesis, and post-remission therapy. AML treatment generally involves chemotherapy, and sometimes involves radiation therapy to relieve AML-induced bone pain. For patients who have relapses or have AML that does not respond to other treatment, bone marrow transplantation (“BMT”) may be required, and can often increase survival.
Certain chromosomal abnormalities are routinely used to determine prognosis in adult AML patients, including t(8;21), t(15;17) or inv(16) suggestive of better prognosis; t(9; 11) used to classify patients at intermediate risk; and inv(3), −5/del(5q), −7/del(7q), t(6;9), abnormalities involving 11q23, or a complex karyotype (three or more cytogenetic aberrations) used to classify patient as being at high risk (Valk et al., New England J of Medicine, 350(16):1617-1628; Bullinger et al., New England J. of Medicine, 350(16):1605-1616 (2004)). However a significant proportion of AML patients do not exhibit such genetic abnormalities. These patients are termed the “normal karyotype” subset of AML patients, and there is currently no consensus for either risk stratification or optimal treatment regimen for this group. A means to provide a prognosis for these patients would likely be of great clinical utility.